We agree with Drs. Lineen and Naimark that the eGFR is an imperfect surrogate for the actual GFR and that decreases in the GFR are not identical to those in the eGFR. The treatment benefit that the TEMPO trial investigators describe may also seem greater when assessed using the eGFR instead of the true GFR, although measuring the latter would have been challenging given the relative large sample size and dispersed geography described in this trial.

The eGFR necessarily introduces regression error. Ideally, we could relate our model inputs (for example, mortality rates, health-related quality of life, and health care costs) to a true rather than estimated GFR, although we note that our model using the eGFR matches the progression rates to end-stage renal disease observed in large cohorts of patients with ADPKD. However, measures of true GFR (for example, inulin or iothalamate clearance) are not without imprecision. Moreover, the true GFR does not encompass the totality of what the kidneys contribute to human health, because kidney function modulates volume and blood pressure, biochemical and hormonal balance, and pro- and anti-inflammatory and oxidant status, among other life-sustaining tasks beyond the filtration of solutes.